Mechanisms Of Cortical Plasticity Research Articles

Neural mechanisms of associative cortical plasticity in cognitive domain: Magnetoencephalographic studies

Acquisition of language semantics is widely believed to be facilitated by biological mechanisms of associative learning [1]. However, current understanding of brain mechanisms underlying learning and memory is primarily based on simple models, including animal models, with mechanisms of learning in the cognitive realm largely unknown. Semantic language learning serves as a compelling example of these cognitive processes, whose brain mechanisms pose a challenge to explanation at the level of basic neural networks. Particularly, many processes underlying such learning still lack clear understanding, including the mechanisms that enable correlational coincidence of neuronal representation required for Hebbian plasticity, the reverberatory replay of the to-be associated representations in working memory, and the involvement of consolidation, among others. We conducted a series of studies modeling the acquisition of semantic knowledge of action-related vocabulary to investigate these questions. We implemented a unique trial-and-error-based procedure for semantic acquisition, in which participants obtained associations between newly introduced pseudowords and actions through active learning. The experimental procedure comprised the delivery of acoustically equivalent pseudowords that were previously unknown to the subjects. Participants were instructed to execute movements of their hands and feet in response to specific pseudowords. Following each trial, participants received either positive or negative feedback depending on their performance. During the learning phase, MEG was recorded, as well as during passive presentations of the same pseudowords before and after learning to control for attention and motor preparation effects. Our analysis involved event-related fields and beta oscillations. Our experiments showed that cortical plasticity related to word learning could be detected immediately after learning, without the need for prolonged consolidation time [2]. We observed two effects during learning that could contribute to Hebbian plasticity by linking auditory speech representations of pseudowords with associated movements. First, we observed the reactivation of auditory speech representations during the initialization of movement. This mechanism apparently creates the conditions for temporal coincidence of activations in two representations, specifically an auditory speech representation and a representation of a motor program. During the learning process, we observed a considerable rise in beta oscillations that occurred during and after action execution. This effect comprised a typical beta-rebound in the sensorimotor regions and a significant surge in beta activity in various associative cortical regions. We postulate that these beta oscillations constitute a reverberation mechanism that reinforces the associative connection and guards it against potential interference [3]. In further experiments, we administered the learning process over two consecutive days with an overnight interval between recordings. We evaluated beta power dynamics during the acquisition of novel pseudowords on day 1 and during task rehearsal following overnight sleep on day 2. Beta event-related synchronization in the frontal regions emerged upon the attainment of the pseudoword learning rules on day 1, and remained unchanged after sleep and subsequent rehearsal on day 2. The prefrontal beta rhythm’s dynamics mirrored the corresponding behavioral changes: subjects executed the task with minimal errors on day 2 upon meeting the learning criterion on day 1. Beta event-related synchronization augmented continuously in the posterior temporal and parietal cortices on day 2 and potentially contributed towards the assimilation of newly-acquired associations in long-term memory. In summary, our research offers fresh perspectives on the intricate neural mechanisms underlying plasticity in the human brain within the cognitive domain.

Transcranial magnetic stimulation combined with endogenous human hippocampal and motor cortical activity enhances memory.

The hippocampus is a fundamental cortical structure in the memory process of encoding, retaining, and recalling information. Transcranial Magnetic Stimulation (TMS) following a Paired Associative Stimulation (PAS) enhances nervous system excitability and promotes cortical plasticity mechanisms by synchronizing two stimuli in the same neural pathway. However, PAS has not been shown to improve memorization capacity yet. Here, we present an innovative protocol stemming from the PAS paradigm, which combines single-pulse TMS to the hippocampus with endogenous hippocampal activity during a working memory (WM) task. 96 volunteers were randomized across one experimental group and three parallel groups (motor cortex stimulation, sham stimulation, and no stimulation) in a single session. This combined-stimuli configuration resulted in an increased memorization capacity in the WM task, which was dependent on the stimulated brain location and subjects' basal memory performance. These results are potentially significant for clinical research on memory dysfunction and its related neurological disorders. Future research on paired associative or combined stimulation is required to unveil stimulation-derived neural mechanisms that enhance the ability to memorize.

Do blind people hear better?

For centuries, anecdotal evidence such as the perfect pitch of the blind piano tuner or blind musician has supported the notion that individuals who have lost their sight early in life have superior hearing abilities compared with sighted people. Recently, auditory psychophysical and functional imaging studies have identified that specific auditory enhancements in the early blind can be linked to activation in extrastriate visual cortex, suggesting crossmodal plasticity. Furthermore, the nature of the sensory reorganization in occipital cortex supports the concept of a task-based functional cartography for the cerebral cortex rather than a sensory-based organization. In total, studies of early-blind individuals provide valuable insights into mechanisms of cortical plasticity and principles of cerebral organization.

Long-term changes in short-interval intracortical facilitation modulate motor cortex plasticity and L-dopa-induced dyskinesia in Parkinson's disease

BackgroundAbnormal glutamatergic neurotransmission in the primary motor cortex (M1) contributes to Parkinson's disease (PD) pathophysiology and is related to l-dopa-induced dyskinesia (LID). We previously showed that short-term treatment with safinamide, a monoamine oxidase type-B inhibitor with anti-glutamatergic properties, improves abnormally enhanced short-interval intracortical facilitation (SICF) in PD patients. ObjectiveTo examine whether a long-term SICF modulation has beneficial effects on clinical measures, including LID severity, and whether these changes parallel improvement in cortical plasticity mechanisms in PD. MethodsWe tested SICF in patients with and without LID before (S0) and after short- (14 days - S1) and long-term (12 months - S2) treatment with safinamide 100 mg/day. Possible changes in M1 plasticity were assessed using intermittent theta-burst stimulation (iTBS). Finally, we correlated safinamide-related neurophysiological changes with modifications in clinical scores. ResultsSICF was enhanced at S0, and prominently in patients with LID. Safinamide normalized SICF at S1, and this effect persisted at S2. Impaired iTBS-induced plasticity was present at S0 and safinamide restored this alteration at S2. There was a significant correlation between the degree of SICF and the amount of iTBS-induced plasticity at S0 and S2. In patients with LID, the degree of SICF at S0 and S2 correlated with long-term changes in LID severity. ConclusionsAltered SICF contributes to M1 plasticity impairment in PD. Both SICF and M1 plasticity improve after long-term treatment with safinamide. The abnormality in SICF-related glutamatergic circuits plays a role in LID pathophysiology, and its long-term modulation may prevent LID worsening over time.

Neural Mechanisms of Associative Cortical Plasticity in Cognitive Domain: MEG Study

Neural Mechanisms of Associative Cortical Plasticity in Cognitive Domain: MEG Study

Occipital repetitive transcranial magnetic stimulation does not affect multifocal visual evoked potentials

BackgroundTo identify mechanisms of cortical plasticity of the visual cortex and to quantify their significance, sensitive parameters are warranted. In this context, multifocal visual evoked potentials (mfVEPs) can make a valuable contribution as they are not associated with cancellation artifacts and include also the peripheral visual field.ObjectiveTo investigate if occipital repetitive transcranial magnetic stimulation (rTMS) can induce mfVEP changes.Methods18 healthy participants were included in a single-blind crossover-study receiving sessions of excitatory, occipital 10 Hz rTMS and sham stimulation. MfVEP was performed before and after each rTMS session and changes in amplitude and latency between both sessions were compared using generalized estimation equation models.ResultsThere was no significant difference in amplitude or latency between verum and sham group.ConclusionWe conclude that occipital 10 Hz rTMS has no effect on mfVEP measures, which is in line with previous studies using full field VEP.

Effects of Cerebellar Theta Burst Stimulation on Contralateral Motor Cortex Excitability in Patients with Alzheimer's Disease.

Although the cerebellum is not among the most renowned brain structures affected in Alzheimer`s disease (AD), recent evidence suggest that it undergoes degenerative changes during the course of the disease. A main neurophysiological feature of AD patients is the remarkable impairment of long term potentiation (LTP)-like cortical plasticity assessed in the primary motor cortex (M1) using theta burst stimulation (TBS) protocols. In healthy conditions, continuous (cTBS) and intermittent TBS (iTBS) of the cerebellum induce respectively long term depression (LTD)-like and LTP-like after effects in the contralateral M1. Here we aimed at examining the effects of cerebellar TBS on contralateral M1 excitability in a sample of 15 AD patients and 12 healthy age matched controls (HS). Motor evoked potentials (MEPs) were obtained in the contralateral M1 before and after cerebellar cTBS and iTBS protocols. As compared to HS, AD patients showed an impairment of LTP-like cortical plasticity mechanisms following cerebellar iTBS. No difference was observed for the cTBS protocol, in which both populations exhibited the expected LTD-like after effect. This study shows that mechanisms of cerebellar-cortical plasticity are impaired in AD. Given its role in high order cognitive functions, new potential therapeutic strategies could be built up in the future to modulate neural activity in the cerebellum in AD.

LTP-like cortical plasticity predicts conversion to dementia in patients with memory impairment

BackgroundNew diagnostic criteria consider Alzheimer’s disease (AD) as a clinico-biological entity identifiable in vivo on the presence of specific patterns of CSF biomarkers. ObjectiveHere we used transcranial magnetic stimulation to investigate the mechanisms of cortical plasticity and sensory-motor integration in patients with hippocampal-type memory impairment admitted for the first time in the memory clinic stratified according to CSF biomarkers profile. MethodsSeventy-three patients were recruited and divided in three groups according to the new diagnostic criteria: 1) Mild Cognitive Impaired (MCI) patients (n = 21); Prodromal AD (PROAD) patients (n = 24); AD with manifest dementia (ADD) patients (n = 28). At time of recruitment all patients underwent CSF sampling for diagnostic purposes. Repetitive and paired-pulse transcranial magnetic stimulation protocols were performed to investigate LTP-like and LTD-like cortical plasticity, short intracortical inhibition (SICI) and short afferent inhibition (SAI). Patients were the followed up during three years to monitor the clinical progression or the conversion to dementia. ResultsMCI patients showed a moderate but significant impairment of LTP-like cortical plasticity, while ADD and PROAD groups showed a more severe loss of LTP-like cortical plasticity. No differences were observed for LTD-like cortical plasticity, SICI and SAI protocols. Kaplan-Meyer analyses showed that PROAD and MCI patients converting to dementia had weaker LTP-like plasticity at time of first evaluation. ConclusionLTP-like cortical plasticity could be a novel biomarker to predict the clinical progression to dementia in patients with memory impairment at prodromal stages of AD identifiable with the new diagnostic criteria based on CSF biomarkers.

Cortical Plasticity in Rehabilitation for Upper Extremity Peripheral Nerve Injury: A Scoping Review.

Poor outcomes after upper extremity peripheral nerve injury (PNI) may arise, in part, from the challenges and complexities of cortical plasticity. Occupational therapy practitioners need to understand how the brain changes after peripheral injury and how principles of cortical plasticity can be applied to improve rehabilitation for clients with PNI. To identify the mechanisms of cortical plasticity after PNI and describe how cortical plasticity can contribute to rehabilitation. PubMed and Embase (1900-2017) were searched for articles that addressed either (1) the relationship between PNI and cortical plasticity or (2) rehabilitative interventions based on cortical plastic changes after PNI. : PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. Articles were selected if they addressed all of the following concepts: human PNI, cortical plasticity, and rehabilitation. Phantom limb pain and sensation were excluded. Sixty-three articles met the study criteria. The most common evidence level was Level V (46%). We identified four commonly studied mechanisms of cortical plasticity after PNI and the functional implications for each. We found seven rehabilitative interventions based on cortical plasticity: traditional sensory reeducation, activity-based sensory reeducation, selective deafferentation, cross-modal sensory substitution, mirror therapy, mental motor imagery, and action observation with simultaneous peripheral nerve stimulation. The seven interventions ranged from theoretically well justified (traditional and activity-based sensory reeducation) to unjustified (selective deafferentation). Overall, articles were heterogeneous and of low quality, and future research should prioritize randomized controlled trials for specific neuropathies, interventions, or cortical plasticity mechanisms. This article reviews current knowledge about how the brain changes after PNI and how occupational therapy practitioners can take advantage of those changes for rehabilitation.

Cortical M1 plasticity and metaplasticity in patients with multiple sclerosis

BackgroundPrevious studies on patients with Multiple Sclerosis (MS) have reported contrasting findings on cortical plasticity of the primary motor cortex and no study has yet evaluated the regulatory mechanisms of cortical plasticity (i.e., metaplasticity) in MS patients. The aim of the present study was to investigate primary motor cortex (M1) plasticity and metaplasticity in patients with MS. MethodsNineteen patients affected by Relapsing-–Remitting MS (RR-MS) and 16 age- and sex-matched healthy controls underwent intermittent Theta Burst Stimulation (iTBS) to evaluate cortical plasticity and iTBS preceded by repetitive index finger movements to evaluate M1 metaplasticity. ResultsIn healthy subjects MEP size significantly increased after iTBS whereas it significantly decreased when repetitive index finger movements preceded iTBS (metaplasticity) (factor PROTOCOL: p < 0.0001; PROTOCOL x TIME interaction: p = 0.001). Conversely, in MS patients MEP size mildly increased, albeit not significantly in both conditions (p > 0.05). In MS patients, percentage changes in MEP size induced by plasticity and metaplasticity protocol were significantly associated to EDSS (p = 0.001) and kinematics of index finger movements (p = 0.01). ConclusionM1 plasticity and metaplasticity are both altered in MS patients. When TBS is used for therapeutic purposes, TBS protocols should be tailored according to the M1 plasticity functional reserve of each MS patient.

Learning of Artificial Sensation Through Long-Term Home Use of a Sensory-Enabled Prosthesis.

Upper limb prostheses are specialized tools, and skilled operation is learned by amputees over time. Recently, neural prostheses using implanted peripheral nerve interfaces have enabled advances in artificial somatosensory feedback that can improve prosthesis outcomes. However, the effect of sensory learning on artificial somatosensation has not been studied, despite its known influence on intact somatosensation and analogous neuroprostheses. Sensory learning involves changes in the perception and interpretation of sensory feedback and may further influence functional and psychosocial outcomes. In this mixed methods case study, we examined how passive learning over 115 days of home use of a neural-connected, sensory-enabled prosthetic hand influenced perception of artificial sensory feedback in a participant with transradial amputation. We examined perceptual changes both within individual days of use and across the duration of the study. At both time scales, the reported percept locations became significantly more aligned with prosthesis sensor locations, and the phantom limb became significantly more extended toward the prosthesis position. Similarly, the participant’s ratings of intensity, naturalness, and contact touch significantly increased, while his ratings of vibration and movement significantly decreased across-days for tactile channels. These sensory changes likely resulted from engagement of cortical plasticity mechanisms as the participant learned to use the artificial sensory feedback. We also assessed psychosocial and functional outcomes through surveys and interviews, and found that self-efficacy, perceived function, prosthesis embodiment, social touch, body image, and prosthesis efficiency improved significantly. These outcomes typically improved within the first month of home use, demonstrating rapid benefits of artificial sensation. Participant interviews indicated that the naturalness of the experience and engagement with the prosthesis increased throughout the study, suggesting that artificial somatosensation may decrease prosthesis abandonment. Our data showed that prosthesis embodiment was intricately related to naturalness and phantom limb perception, and that learning the artificial sensation may have modified the body schema. As another indicator of successfully learning to use artificial sensation, the participant reported the emergence of stereognosis later in the study. This study provides the first evidence that artificial somatosensation can undergo similar learning processes as intact sensation and highlights the importance of sensory restoration in prostheses.

Withdrawal from acute medication normalises short-term cortical synaptic potentiation in medication overuse headache

To study the effects of a standard acute medication withdrawal program on short-term cortical plasticity mechanisms in patients with medication overuse headache (MOH). Thirteen patients with MOH and 16 healthy volunteers underwent repetitive transcranial magnetic stimulation (rTMS) over the left motor cortex; in patients with MOH, recordings were performed before and after a 3-week medication withdrawal program. Ten trains of 10 stimuli each (120% resting motor threshold) were delivered at 1Hz or 5Hz in two separate sessions in a randomised order. Motor evoked potential (MEP) amplitudes were measured from the right first dorsal interosseous muscle and the slope of the linear regression line from the first to the tenth stimuli was calculated for each participant. All subjects exhibited MEP amplitude inhibition in response to 1Hz rTMS. Alternatively, the 5-Hz trains of rTMS inhibited rather than potentiated MEP amplitudes in patients with MOH. The physiological potentiating effect of 5Hz rTMS on MEP amplitudes was restored after drug withdrawal and in proportion with the percentage reduction in monthly headache days in patients with MOH. The results suggest that acute medication withdrawal normalises brain responses in patients with MOH. Clinical improvements after medication withdrawal may reflect the reversal of neurophysiological dysfunction. Accordingly, medication withdrawal should be offered to patients with MOH as early as possible in order to prevent the development of more pronounced alterations in brain plasticity.

Thumbs up: Imagined hand movements counteract the adverse effects of post-surgical hand immobilization. Clinical, behavioral, and fMRI longitudinal observations.

Motor imagery (M.I.) training has been widely used to enhance motor behavior. To characterize the neural foundations of its rehabilitative effects in a pathological population we studied twenty-two patients with rhizarthrosis, a chronic degenerative articular disease in which thumb-to-fingers opposition becomes difficult due to increasing pain while the brain is typically intact. Before and after surgery, patients underwent behavioral tests to measure pain and motor performance and fMRI measurements of brain motor activity.After surgery, the affected hand was immobilized, and patients were enrolled in a M.I. training. The sample was split in those who had a high compliance with the program of scheduled exercises (T+, average compliance: 84%) and those with low compliance (T−, average compliance: 20%; cut-off point: 55%). We found that more intense M.I. training counteracts the adverse effects of immobilization reducing pain and expediting motor recovery. fMRI data from the post-surgery session showed that T+ patients had decreased brain activation in the premotor cortex and the supplementary motor area (SMA); meanwhile, for the same movements, the T− patients exhibited a reversed pattern. Furthermore, in the post-surgery fMRI session, pain intensity was correlated with activity in the ipsilateral precentral gyrus and, notably, in the insular cortex, a node of the pain matrix.These findings indicate that the motor simulations of M.I. have a facilitative effect on recovery by cortical plasticity mechanisms and optimization of motor control, thereby establishing the rationale for incorporating the systematic use of M.I. into standard rehabilitation for the management of post-immobilization syndromes characteristic of hand surgery.

Impaired Spike Timing Dependent Cortico-Cortical Plasticity in Alzheimer's Disease Patients.

Mechanisms of cortical plasticity have been recently investigated in Alzheimer's disease (AD) patients with transcranial magnetic stimulation protocols showing a clear impairment of long-term potentiation (LTP) cortical-like plasticity mechanisms. We aimed to investigate mechanisms of cortico-cortical spike-timing dependent plasticity (STDP) in AD patients investigating the connections between posterior parietal cortex (PPC) and primary motor cortex (M1). We used a cortico-cortical paired associative stimulation (cc-PAS) protocol to repeatedly activate the connection between PPC and M1 of the left-dominant hemisphere in a sample of fifteen AD patients and ten age-matched healthy subjects. PPC transcranial magnetic stimulation preceded (ccPAS +5) or followed M1 stimulation (ccPAS - 5) by 5 ms. Motor-evoked potentials (MEPs) were collected to assess the time course of the after effects of cc-PAS protocol measuring MEP amplitude as index of cortico-cortical associative plasticity. In healthy subjects, ccPAS - 5 protocol induced the expected long-lasting increase of MEP amplitude compatible with LTP-like cortical plasticity while PAS +5 protocol induced the opposite effect. AD patients did not show any significant modification of the amplitude of MEP after both ccPAS protocols. Our study shows that in AD patients the time-locked activation of human cortico-cortical connections is not able to form STDP, reflecting an impairment of a multi-factor plasticity process.

LTP-like cortical plasticity is associated with verbal memory impairment in Alzheimer's disease patients

BackgroundAlzheimer's disease (AD) is characterized by a primary impairment of long-term declarative memory caused by deposition of misfolded protein aggregates. Experimental studies showed that AD neuropathological alterations impair synaptic plasticity and memory performance. Transcranial Magnetic Stimulation protocols have been recently introduced to investigate altered mechanisms of cortical plasticity in AD patients. AimTo investigate relationship between Long-Term Potentiation (LTP)-like cortical plasticity and patients’ neuropsychological performance. MethodsWe applied intermittent theta burst stimulation and extensive neuropshycological battery in 75 newly diagnosed AD patients. ResultsWe found that LTP-like cortical plasticity impairment is selectively associated to a less efficient verbal memory (r = 0.45; p = 0.002), but not to other cognitive functions, independently from biomarkers and other demographic and clinical factors. ConclusionThese findings suggest that LTP-like cortical plasticity may represent a neurophysiological surrogate of memory in AD patients by evaluating the weight of pathological changes responsible for cognitive dysfunction.

Dysregulation of auditory neuroplasticity in schizophrenia

Schizophrenia is a complex brain syndrome characterized by an array of positive symptoms (delusions, hallucinations, disorganized speech), negative symptoms (alogia, apathy, avolition) and cognitive impairments (memory, executive functions). Although investigations of the cognitive deficits in schizophrenia have primarily concentrated on disturbances affecting higher-order cognitive processes, there is an increasing realization that schizophrenia also affects early sensory processing, which might, in fact, play a significant role in the development of higher-order cognitive impairments. Recent evidence suggests that many of these early sensory processing impairments possibly arise from a dysregulation of plasticity regulators in schizophrenia, resulting in either reduced plasticity or excessive unregulated plasticity. The purpose of the present manuscript is to provide a concise overview of how the dysregulation of cortical plasticity mechanisms contributes to schizophrenia symptoms with an emphasis on auditory dysplasticity and to discuss its relevance for treatment outcomes. The idea that plasticity mechanisms are not constrained only within sensitive periods suggests that many functional properties of sensory neurons can be altered throughout the lifetime.

Neuregulin directed molecular mechanisms of visual cortical plasticity.

Experience-dependent critical period (CP) plasticity has been extensively studied in the visual cortex. Monocular deprivation during the CP affects ocular dominance, limits visual performance, and contributes to the pathological etiology of amblyopia. Neuregulin-1 (NRG1) signaling through its tyrosine kinase receptor ErbB4 is essential for the normal development of the nervous system and has been linked to neuropsychiatric disorders such as schizophrenia. We discovered recently that NRG1/ErbB4 signaling in PV neurons is critical for the initiation of CP visual cortical plasticity by controlling excitatory synaptic inputs onto PV neurons and thus PV-cell mediated cortical inhibition that occurs following visual deprivation. Building on this discovery, we review the existing literature of neuregulin signaling in developing and adult cortex and address the implication of NRG/ErbB4 signaling in visual cortical plasticity at the cellular and circuit levels. NRG-directed research may lead to therapeutic approaches to reactivate plasticity in the adult cortex.

Clinical and electrophysiological impact of repetitive low-frequency transcranial magnetic stimulation on the sensory-motor network in patients with restless legs syndrome.

Background:Based on the hyperexcitability and disinhibition observed in patients with restless legs syndrome (RLS) following transcranial magnetic stimulation (TMS), we conducted a study with low-frequency repetitive TMS (rTMS) over the primary motor (M1) and somatosensory cortical areas (S1) in patients with RLS.Methods:A total of 13 right-handed patients and 10 age-matched controls were studied using clinical scales and TMS. Measurements included resting motor threshold (rMT), motor-evoked potentials (MEPs), cortical silent period (CSP), and central motor conduction time (CMCT). A single evening session of rTMS (1 Hz, 20 trains, 50 stimuli each) was administered over the left M1, left S1, and sham stimulation over M1 in a random order. Clinical and TMS measures were repeated after each stimulation modality.Results:Baseline CSP was shorter in patients than in controls and remained shorter in patients for both motor and somatosensory stimulation. The patients reported a subjective improvement of both initiating and maintaining sleep the night after the rTMS over S1. Patients exhibited a decrease in rMT after rTMS of S1 only, although the effect was smaller than in controls. MEP latency and CMCT changed only in controls after stimulation. Sham stimulation was without effect on the observed variables.Conclusions:rTMS on S1-M1 connectivity alleviated the sensory–motor complaints of RLS patients. The TMS indexes of excitation and inhibition indicate an intracortical and corticospinal imbalance, mainly involving gamma-aminobutyric acid (GABA)ergic and glutamatergic circuitries, as well as an impairment of the short-term mechanisms of cortical plasticity. The rTMS-induced activation of the dorsal striatum with the consequent increase of dopamine release may have contributed to the clinical and neurophysiological outcome.

Predictive Place-Cell Sequences for Goal-Finding Emerge from Goal Memory and the Cognitive Map: A Computational Model.

Hippocampal place-cell sequences observed during awake immobility often represent previous experience, suggesting a role in memory processes. However, recent reports of goals being overrepresented in sequential activity suggest a role in short-term planning, although a detailed understanding of the origins of hippocampal sequential activity and of its functional role is still lacking. In particular, it is unknown which mechanism could support efficient planning by generating place-cell sequences biased toward known goal locations, in an adaptive and constructive fashion. To address these questions, we propose a model of spatial learning and sequence generation as interdependent processes, integrating cortical contextual coding, synaptic plasticity and neuromodulatory mechanisms into a map-based approach. Following goal learning, sequential activity emerges from continuous attractor network dynamics biased by goal memory inputs. We apply Bayesian decoding on the resulting spike trains, allowing a direct comparison with experimental data. Simulations show that this model (1) explains the generation of never-experienced sequence trajectories in familiar environments, without requiring virtual self-motion signals, (2) accounts for the bias in place-cell sequences toward goal locations, (3) highlights their utility in flexible route planning, and (4) provides specific testable predictions.

Transcriptional mapping of the primary somatosensory cortex upon sensory deprivation.

Experience-dependent plasticity (EDP) is essential for anatomical and functional maturation of sensory circuits during development. Although the principal synaptic and circuit mechanisms of EDP are increasingly well studied experimentally and computationally, its molecular mechanisms remain largely elusive. EDP can be readily studied in the rodent barrel cortex, where each “barrel column” preferentially represents deflections of its own principal whisker. Depriving select whiskers while sparing their neighbours introduces competition between barrel columns, ultimately leading to weakening of intracortical, translaminar (i.e., cortical layer (L)4-to-L2/3) feed-forward excitatory projections in the deprived columns. The same synapses are potentiated in the neighbouring spared columns. These experience-dependent alterations of synaptic strength are thought to underlie somatosensory map plasticity. We used RNA sequencing in this model system to uncover cortical-column and -layer specific changes on the transcriptome level that are induced by altered sensory experience. Column- and layer-specific barrel cortical tissues were collected from juvenile mice with all whiskers intact and mice that received 11–12 days of long whisker (C-row) deprivation before high-quality RNA was purified and sequenced. The current dataset entails an average of 50 million paired-end reads per sample, 75 base pairs in length. On average, 90.15% of reads could be uniquely mapped to the mm10 reference mouse genome. The current data reveal the transcriptional changes in gene expression in the barrel cortex upon altered sensory experience in juvenile mice and will help to molecularly map the mechanisms of cortical plasticity.